Studies have shown that human neutrophils pre-exposed to chemotactic factors show enhanced bactericidal activity and oxidative metabolism in response to a second stimulus such as phorbol myristate acetate (PMA), Con A or opsonized zymosan. Current studies show that this is due to a chemotactic factor mediated priming of the membrane associated oxidase. Pre-exposure of neutrophils to chemotactic factor results in an increase in the Vmax and a decrease in the Km of microsomal PMA stimulated NADPH dependent oxidase activity. Studies are underway to determine the mechanism of priming. Additional work indicates that this same type of enhancement occurs in vivo in the inflamed joints of patients with rheumatoid arthritis. Studies show that neutrophils from synovial effusions show enhanced PMA stimulated chemiluminescence and that normal PMNs elicit a similar enhanced response when incubated with the synovial fluid from these patients. Studies of neutrophil chemotaxis to f-met-leu-phe have shown that this response is impaired by IgA paraproteins from patients with myeloma. Work in progress indicates that this is due to a non-competative inhibition of f-met-leu-phe receptors on the neutrophil surface. Additional studies on the mechanism of blocking are underway. Finally, the chemotactic response to various factors is not restricted to neutrophils, and current studies show that human lymphocytes migrate in response to f-met-leu-phe, C5a and casein. the response of lymphocyte subpopulations (T and non-T cells) differs with respect to these factors. T cells respond to casein and C5a while non-T cells respond to f-met-leu-phe and C5a. Additional studies to clarify these observations and further divide lymphocyte subpopulations are underway.